We have examined the effect of brief exposure of the rat sciatic nerve to high concentrations of colchicine. Application of 4-15 mM colchicine caused no drop in the RMP of the EDL muscle but did cause an increase in its ACh sensitivity. Application of 30-60 mM colchicine caused both a drop in RMP and an increase in ACh sensitivity. Application of 120-240 mM colchicine caused an impairment of neuromuscular transmission as well as a drop in RMP and an increase in ACh sensitivity. Control experiments indicate that the changes in RMP and ACh sensitivity caused by 30-60 mM colchicine were not due to a decrease in muscle activity or to a direct effect of colchicine on muscle. 60 mM colchicine as applied in these experiments did cause a block of axoplasmic transport and this block behaved as one would predict if it is responsible for the drop in RMP and the increase in ACh sensitivity. We interpret these experiments to mean that the application of appropriate concentrations of colchicine to rat sciatic nerve blocks the axoplasmic transport of trophic substances necessary for the maintenance of normal RMP and ACh sensitivity in the EDL muscle.